Idiopathic inflammatory myopathy (polymyositis, dermatomyositis, and related disorders) is a family of inflammatory diseases in which disease- specific autoantibodies occur and for which there is considerable indirect evidence pointing to a viral etiology. We have over the past several years, seen and studied and collected serum, blood, and muscle specimens from well over 450 patients suspected of having myositis. We have collected epidemiologic information on many patients. We have cloned, sequenced, and expressed histidyl-TRNA synthetase HRS, the principal target autoantigen in idiopathic polymyositis and dermatomyositis and are analyzing its structure and promoter. We have extended the analysis of HLA antigens in the sets of myositis patients defined by autoantibodies using the sequence specific oligonucleotide hybridization/PCR method. We have analyzed promoter activity of the HRS gene and are currently investigating translational control of its synthesis. We have successfully obtained high level expression of HRS, purified it, and crystallized it. A sensitive, specific, stable ELISA has been developed and a patent applied for. In collaboration with Dr. Terry O'Hanlan and Dr. Frederick Miller, we have analyzed T cell receptor usage in the muscle of some patients with myositis.